Phase 1 Combination Study of MM-151 With MM-121, MM-141, or Trametinib

A Phase 1 Multi Arm Study Evaluating the Safety, Pharmacology and Preliminary Activity of the Co-Administration of MM-151 With Seribantumab (MM-121), Istiratumab (MM-141), or Trametinib in Biomarker-selected Cancer Patients

This is a Phase 1 open-label, dose-escalation trial using "3+3" design, evaluating MM-151 co-administration with MM-121, MM-141, and trametinib at varying dose levels.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer; Squamous Cell Carcinoma of the Head and Neck; Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: MM-151; Drug: MM-121; Drug: trametinib; Drug: MM-141

Detailed Description

This is a two-part Phase 1, non-randomized, open-label study of MM-151 plus MM-121, MM-141, or trametinib in patients with advanced, heregulin-positive lung, head and neck, and colorectal cancers. In part 1 of the study, cohorts of 3 or more patients will be treated at escalating doses of MM-151 in combination with MM-121, MM-141, and trametinib until a maximum tolerated combination dose for each combination is identified. In part 2 of the study, patients will be treated with the combination dose identified in part 1 of the study.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Georgia
    • Sandy Springs, Georgia, United States, 30342
      • Northside Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must be >18 years of age
• Patients must be able to provide informed consent
• Willing to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of any study therapy). This applies to women of childbearing potential as well as fertile men and their partners
• Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy, up to CTCAE grade 1
• Patients must have either heregulin-positive cancer, cancer with RAS mutation, IGF-1 positive cancer, or RAS wild type cancer.

Exclusion Criteria:

• Patients who are pregnant or lactating
• Patients who have an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients with tumor fever may be enrolled.)
• Patients with untreated (primary) or symptomatic CNS (primary or metastatic) malignancies; patients with CNS metastases who have undergone surgery or radiotherapy or who have been on a stable dose of corticosteroids for at least 2 weeks and whose disease is stable prior to the first scheduled day of dosing will be eligible for the trial.
• Patients who have received other recent antitumor therapy including any standard chemotherapy or radiation within 14 days (and having passed the time of any actual or anticipated toxicities) prior to the first scheduled dose of the study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MM-151+MM-121 Dose Escalation; MM-151 and MM-121 dose escalation in lung, head and neck, and colorectal cancers	Drug: MM-151; MM-151; Drug: MM-121; MM-121
Experimental: MM-151+ trametinib Dose Escalation; MM-151 and trametinib dose escalation in lung, head and neck, and colorectal cancers.	Drug: MM-151; MM-151; Drug: trametinib; trametininb; Other Names: MEKINIST
Experimental: MM-151+MM-141 Dose Escalation; MM-151 and MM-141 dose escalation in lung, head and neck, and colorectal cancers	Drug: MM-151; MM-151; Drug: MM-141; MM-141
Experimental: MM-151+trametinib Dose Escalation; MM-151 and trametinib dose escalation in lung, head and neck, and colorectal cancers.	Drug: MM-151; MM-151; Drug: trametinib; trametininb; Other Names: MEKINIST
Experimental: Colorectal cancer Expansion; Doses established in part 1 of the study	Drug: MM-151; MM-151; Drug: MM-121; MM-121; Drug: trametinib; trametininb; Other Names: MEKINIST; Drug: MM-141; MM-141
Experimental: Head and neck Expansion; Doses established in part 1 of the study	Drug: MM-151; MM-151; Drug: MM-121; MM-121; Drug: trametinib; trametininb; Other Names: MEKINIST; Drug: MM-141; MM-141

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To find a phase II dose of MM-151 in combination with MM-121, MM-141, and trametinib based on maximum tolerated dose (MTD) in patients with lung, head and neck, and colorectal cancers	1.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of dose limiting toxicities (DLTs) within a group	1.5 years
Adverse event profile of MM-151 in combination with MM-121, MM-141, and trametinib	1.5 years
Objective response to MM-151 in combination with MM-121, MM-141, and trametinib based on RECIST	1.5 years

Collaborators and Investigators

• Sponsor: Merrimack Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): October 5, 2016
• Study Completion (Actual): October 5, 2016

Study Registration Dates

• First Submitted: August 31, 2015
• First Submitted That Met QC Criteria: August 31, 2015
• First Posted (Estimate): September 2, 2015

Study Record Updates

• Last Update Posted (Actual): September 5, 2017
• Last Update Submitted That Met QC Criteria: August 31, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Cancer; EGFR; Phase I; Oncology; KRAS; IGF-1; NRAS; ErbB3; Heregulin-positive; MEKinhibitor; IGF-1R inhibitor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Trametinib
• Other Study ID Numbers: MM-151-01-01-02